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International research team discovers key to blood pressure control

Findings believed to have broad applications to human physiology and
disease
THUNDER BAY, ON, Oct. 23 /CNW/ - An international team of scientists has
discovered that cells inside the blood vessels of mice - as well as in people
- naturally produce hydrogen sulfide or H2S, a gas with the smell of rotten
eggs, and this gas controls blood pressure. The research team comprises
scientists from Lakehead University in Ontario, University of Saskatchewan,
and Johns Hopkins.
Having discovered that hydrogen sulfide, or H2S, is produced in the thin,
endothelial lining of blood vessels, the researchers report today in Science
that H2S regulates blood pressure by relaxing blood vessels. As the newest
member of a family of so-called "gasotransmitters," this messenger molecule is
akin in function, if not form, to chemical signals like nitric oxide,
dopamine, and acetylcholine that relay signals between nerve cells, and excite
or put the brakes on mind-brain activities.
According to Dr. Rui Wang, M.D., Ph. D, and Vice President (Research) of
Lakehead University and principal author of the paper, "It's difficult to
overestimate the biological importance of hydrogen sulfide or its implications
in hypertension as well as diabetes and neurodegenerative diseases. In fact,
most human diseases probably have something to do with gasotransmitters."
"Now that we know hydrogen sulfide's role in regulating blood pressure,
it may be possible to design drug therapies that enhance its formation as an
alternative to the current methods of treatment for hypertension," says Johns
Hopkins neuroscientist Solomon H. Snyder, M.D., a co-corresponding author of
the paper.
Conducting their investigations using mice missing a gene for an enzyme
known as CSE, long suspected as responsible for making H2S, the researchers
first measured hydrogen sulfide levels in a variety of tissues in the
CSE-deficient mice and compared them to normal mice. The researchers found
that the gas was largely depleted in the cardiovascular systems of the altered
mice, engineered by Rui Wang and Lingyun Wu, M.D., Ph.D., of the University of
Saskatchewan, Canada, whereas normal mice had higher levels -- clear evidence
that hydrogen sulfide is normally made by mammalian tissues using CSE.
Next, the scientists applied tiny cuffs to the tails of the mice and
measured their blood pressure, noting systolic blood pressure spikes of almost
18 mmHg higher in animals lacking CSE compared with normal mice. In humans the
healthiest adult systolic pressure is 120 mmHg or less, and high blood
pressure is defined as 140 mmHg or more.
Finally, the team tested how blood vessels of CSE-deficient mice
responded to the chemical neurotransmitter methacholine, known to relax normal
blood vessels. The blood vessels of the altered mice relaxed hardly at all,
indicating that hydrogen sulfide was largely responsible for relaxation.
Because gasotransmitters are highly conserved in mammals, the findings of
the research are believed to have broad applications to human physiology and
disease.
"In terms of relaxing blood vessels, it looks like hydrogen sulfide might
be as important as nitric oxide," Snyder says, referring to the first
gasotransmitter that was discovered two decades ago to regulate blood
pressure.
Just because these two gas molecules perform similar functions doesn't
mean they're redundant, says Wang. "Nature has added on layer upon layer of
complexity to provide a better and tighter control of body function - in this
case, of blood pressure."
Although CSE, the enzyme that activates hydrogen sulfide, was
characterized more than half a century ago, the new work is the first to
reveal that its trigger works similarly and involves the same molecules as the
trigger for nitric oxide, thus putting into place the final piece of the
picture puzzle showing how hydrogen sulfide regulates blood pressure by
relaxing blood vessels.
The research was supported by grants from the U.S. Public Health Service
and the Canadian Institutes of Health Research (CIHR) as well as a Research
Scientist Award from CIHR.
Authors of the paper are Guangdong Yang, Lingyun Wu, Bo Jiang, Wei Yang,
Jiansong Qi, Kun Cao, Qinghe Meng, all of the University of Saskatchewan,
Canada; Rui Wang and Shengming Zhang of Lakehead University, Canada; and Asif
K. Mustafa, Weitong Mu, and Snyder, all of Hopkins.
On the Web:
http://www.sciencemag.org
Media Interviews: Dr. Rui Wang is available for interview Monday and
Tuesday, October 27 and 28 for a limited time; to arrange please contact Lisa
Pelot, Communications Officer, 807-343-8177 or commun@lakeheadu.ca.
About Lakehead
Lakehead is a comprehensive university with a reputation for innovative
programs and cutting-edge research. With a main campus located in Thunder Bay,
Ontario and a campus in Orillia, Ontario, Lakehead has over 7,500 students and
2,000 faculty and staff, and is home to the west campus of the Northern
Ontario School of Medicine. In 2006, Research Infosource Inc. named Lakehead
University Canada's Research University of the Year in the undergraduate
category. For more information on Lakehead University, visit www.lakeheadu.ca

For further information:

For further information: Eleanor Abaya, Director of Communications,
(807) 343-8372 or eleanor.abaya@lakeheadu.ca